This research seeks to study the cell-mediated immune response of mice to endogenous AKR leukemia viruses and syngeneic tumors induced by these viruses. H-2-restricted cytotoxic T-cell responses, T-cell proliferative responses, and cellular responses resulting in the production of the nonspecific soluble mediator, interleukin-2 (IL-2), will be examined. The specificity of the H-2Kb-restricted cytotoxic T-cell response to Gross cell surface, antigen-expressing tumor cells will be probed in a variety of ways including the use of an unsusceptible variant subclone (cl.18-5) of the susceptible AKR.H-2bSL1 tumor. The possibility that the target antigens recognized by such cytotoxic T cells may represent "preleukemic" antigens found on normal cells of leukemia-prone mice also will be addressed. The apparent requirement for stimulation with additional antigens other than the target antigens to induce these cellular immune responses will be examined to determine the nature of such required antigens and the cellular basis for their involvement. The genetics of responsiveness, including the effects of loci controlling virus production and/or viral antigen expression as well as loci linked to the H-2 complex, is also an area of intended research. Specifically, the possibility that genes mapping within H-2 and controlling cellular immune responses may exist and their relationship to known loci controlling resistance to leukemia will be tested. Indeed, recent studies have indicated that anti-AKR/Gross leukemia virus cytotoxic T-lymphocyte responses are under multigene control with at least three loci involved. One of these is H-2, where H-2b and H-2k define responder and nonresponder haplotypes, respectively. Although presence of dominant H-2b encoded immune response gene(s) is thus necessary, it is not sufficient for cytotoxic T-cell development. Thus, AKR.H-2b mice are nonresponders. Because AKR.H-2b:Fv-1b double congenics and B6.Fv-1n congenics are responders, however, it appears that Fv-1n allelles can override the positive effects of H-2b by interacting with one or more loci of the "high leukemic" AKR background. The mechanism of this negative epistatic control by Fv-1n appears to relate to its permissiveness in allowing the spread of infection by endogenous N-ecotropic AKR leukemia virus with concommitant expression of viral antigens by normal cells and ensuing specific immunologic tolerance. (SR)